Androgen Deprivation Therapy for Prostatic Cancer in Patients With Torsades de Pointes.
Torsades de Pointes
androgen deprivation therapy
prostatic cancer
sudden death
testosterone
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2020
2020
Historique:
received:
20
01
2020
accepted:
27
04
2020
entrez:
2
6
2020
pubmed:
2
6
2020
medline:
2
6
2020
Statut:
epublish
Résumé
Men normally have shorter heart rate-corrected QT interval (QTc) than women, at least in part due to accelerating effects of testosterone on ventricular repolarization. Accumulating data suggest that androgen-deprivation therapy (ADT) used for the treatment of prostatic cancer, may increase Torsades de Pointes (TdP) risk by prolonging QTc. However, the evidence for such an association is currently limited to few case reports, in most cases deriving from the analysis of uncontrolled sources such as pharmacovigilance databases. To better determine the clinical impact of ADT on TdP development, we examined the prevalence of this therapy in a consecutive cohort of 66 TdP patients, prospectively collected over a ~10 years period. We found and described four patients who were under ADT for prostatic cancer when TdP occurred, and in two cases degenerated to cardiac arrest. Notably, in this unselected population, ADTs unexpectedly represented the second most frequently administered QT-prolonging medication in males (4/24, 17%), after amiodarone. Moreover, in the ADT patients, a blood withdrawal was performed within 24 h from TdP/marked QTc prolongation occurrence and circulating concentration of androgens and gonadothropins were measured. As expected, all cases showed markedly reduced testosterone levels (total, free, and available). We provide evidence that a significant proportion of patients developing TdP were under treatment with ADT for prostatic cancer, thus confirming the clinical relevance of previous pharmacovigilance signals. An accurate assessment of the arrhythmic risk profile should be included in the standard of care of prostatic cancer patients before starting ADT.
Sections du résumé
BACKGROUND
BACKGROUND
Men normally have shorter heart rate-corrected QT interval (QTc) than women, at least in part due to accelerating effects of testosterone on ventricular repolarization. Accumulating data suggest that androgen-deprivation therapy (ADT) used for the treatment of prostatic cancer, may increase Torsades de Pointes (TdP) risk by prolonging QTc. However, the evidence for such an association is currently limited to few case reports, in most cases deriving from the analysis of uncontrolled sources such as pharmacovigilance databases.
OBJECTIVE
OBJECTIVE
To better determine the clinical impact of ADT on TdP development, we examined the prevalence of this therapy in a consecutive cohort of 66 TdP patients, prospectively collected over a ~10 years period.
METHODS AND RESULTS
RESULTS
We found and described four patients who were under ADT for prostatic cancer when TdP occurred, and in two cases degenerated to cardiac arrest. Notably, in this unselected population, ADTs unexpectedly represented the second most frequently administered QT-prolonging medication in males (4/24, 17%), after amiodarone. Moreover, in the ADT patients, a blood withdrawal was performed within 24 h from TdP/marked QTc prolongation occurrence and circulating concentration of androgens and gonadothropins were measured. As expected, all cases showed markedly reduced testosterone levels (total, free, and available).
CONCLUSION
CONCLUSIONS
We provide evidence that a significant proportion of patients developing TdP were under treatment with ADT for prostatic cancer, thus confirming the clinical relevance of previous pharmacovigilance signals. An accurate assessment of the arrhythmic risk profile should be included in the standard of care of prostatic cancer patients before starting ADT.
Identifiants
pubmed: 32477142
doi: 10.3389/fphar.2020.00684
pmc: PMC7239032
doi:
Types de publication
Journal Article
Langues
eng
Pagination
684Informations de copyright
Copyright © 2020 Lazzerini, Bertolozzi, Acampa, Cantara, Castagna, Pieragnoli, D’Errico, Rossi, Bisogno, El-Sherif, Boutjdir, Laghi-Pasini and Capecchi.
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